JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases.

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

Quantitative Techniques of Ultrasonography in the Assessment of Femoropopliteal Atherosclerotic Lesions Using Peak Systolic Velocity Ratio: Results From the TURN-UP Study.

PURPOSE: Duplex ultrasound (DUS)-measured peak systolic velocity ratios (PSVRs) are commonly used to evaluate arterial stenosis in lower extremity artery disease (LEAD). However, these measurement methods have not yet been standardized. This study aimed to reveal the influence of measuring methods on PSVR values. METHODS: A 132 femoropopliteal lesions with PSVR ranging from 1.5 to 3.5 evaluated using method A (angle correction 60°, the direction of blood flow, the no or few atherosclerotic changes closest to the lesion proximal side was defined as the nonstenotic area) were included. The following 4 different methods were then compared with method A: method B, angle correction 45°; method C, angle correction 60° measured along the vessel wall; D, angle correction 60°, with the nonstenotic area the lowest peak systolic velocity area; and E, angle correction 60°, with the reference point fixed at 2 cm proximal to the target lesion area. The difference in PSVR values was analyzed using the Bland-Altman method. RESULTS: The mean PSVR value measured by method A was 2.27±0.51, those measured by methods B, C, D, and E were 2.21±0.55, 2.31±0.66, 2.34±0.63, and 2.11±0.63, respectively. The 95% prediction intervals of the differences in PSVR measurements versus A were -0.64 to +0.53 for method B, -0.59 to +0.68 for method C, -0.77 to +0.91 for method D, and -1.12 to +0.79 for method E. CONCLUSION: PSVR values considerably differed between measuring methods. PSVR values by DUS are largely dependent on the measurement methods, which could considerably affect the judgment of LEAD. CLINICAL IMPACT: Due to differences in several DUS measurement methods, the PSVR results could be changed. Therefore, to need further investigations and unification of measurement method.

Serum anti-PCK1 antibody levels are a prognostic factor for patients with diabetes mellitus.

BACKGROUND: Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM), and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy. METHODS: Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples. RESULTS: Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular disease than in healthy donors, but not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients. CONCLUSIONS: Serum anti-PCK1 antibody levels were found to be associated with DM. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.

R3hdml regulates satellite cell proliferation and differentiation.

In this study, we identified a previously uncharacterized skeletal satellite cell-secreted protein, R3h domain containing-like (R3hdml). Expression of R3hdml increases during skeletal muscle development and differentiation in mice. Body weight and skeletal muscle mass of R3hdml knockout (KO) mice are lower compared to control mice. Expression levels of cell cycle-related markers, phosphorylation of Akt, and expression of insulin-like growth factor within the skeletal muscle are reduced in R3hdml KO mice compared to control mice. Expression of R3hdml increases during muscle regeneration in response to cardiotoxin (CTX)-induced muscle injury. Recovery of handgrip strength after CTX injection was significantly impaired in R3hdml KO mice, which is rescued by R3hdml. Our results indicate that R3hdml is required for skeletal muscle development, regeneration, and, in particular, satellite cell proliferation and differentiation.

Low dose red yeast rice with monacolin K lowers LDL cholesterol and blood pressure in Japanese with mild dyslipidemia: A multicenter, randomized trial.

BACKGROUND AND OBJECTIVES: Red yeast rice contains monacolin K, an inhibitor of cholesterol synthesis, and gamma-aminobutyric acid, a neurotransmitter. The daily dose of red yeast rice and monacolin K in previous studies was relatively high; therefore, there were safety concerns. We aimed to examine the effects of low daily dose red yeast rice on arteriosclerosis in patients with mild dyslipidemia. METHODS AND STUDY DESIGN: Eighteen patients without known cardiovascular disease and unsatisfactory low-density lipoprotein cholesterol (3.96±0.19 mmol/L) controlled only by diet therapy were randomly allocated to receive low dose red yeast rice (200 mg/day) containing 2 mg monacolin K or diet therapy alone for 8 weeks. The primary outcome was the absolute change in low-density lipoprotein cholesterol. Secondary outcomes included total cholesterol, apolipoprotein B, and blood pressure. RESULTS: Low-density lipoprotein cholesterol decreased significantly in the red yeast rice group than in the diet therapy group (median [interquartile range]: control -0.20 [-0.62, 1.19] mmol/L vs. red yeast rice -0.96 [-1.05, -0.34] mmol/L, p=0.030). The red yeast rice group also exhibited significant decreases in total cholesterol, apolipoprotein B, and blood pressure. No severe treatment-related adverse effects on muscles, liver, or renal function were observed. CONCLUSIONS: We found that patients in the red yeast rice group exhibited significant reductions in lowdensity lipoprotein cholesterol, total cholesterol, apolipoprotein B, and blood pressure without any recognised adverse effect. This suggests that low daily dose red yeast rice could reduce cardiovascular risk in patients with dyslipidemia.

Aspergillus Sydowii Marine Fungal Bloom in Australian Coastal Waters, Its Metabolites and Potential Impact on Symbiodinium Dinoflagellates.

Dust has been widely recognised as an important source of nutrients in the marine environment and as a vector for transporting pathogenic microorganisms. Disturbingly, in the wake of a dust storm event along the eastern Australian coast line in 2009, the Continuous Plankton Recorder collected masses of fungal spores and mycelia (~150,000 spores/m³) forming a floating raft that covered a coastal area equivalent to 25 times the surface of England. Cultured A. sydowii strains exhibited varying metabolite profiles, but all produced sydonic acid, a chemotaxonomic marker for A. sydowii. The Australian marine fungal strains share major metabolites and display comparable metabolic diversity to Australian terrestrial strains and to strains pathogenic to Caribbean coral. Secondary colonisation of the rafts by other fungi, including strains of Cladosporium, Penicillium and other Aspergillus species with distinct secondary metabolite profiles, was also encountered. Our bioassays revealed that the dust-derived marine fungal extracts and known A. sydowii metabolites such as sydowic acid, sydowinol and sydowinin A adversely affect photophysiological performance (Fv/Fm) of the coral reef dinoflagellate endosymbiont Symbiodinium. Different Symbiodinium clades exhibited varying sensitivities, mimicking sensitivity to coral bleaching phenomena. The detection of such large amounts of A. sydowii following this dust storm event has potential implications for the health of coral environments such as the Great Barrier Reef.

Australian dust storm associated with extensive Aspergillus sydowii fungal "bloom" in coastal waters.

A massive central Australian dust storm in September 2009 was associated with abundant fungal spores (150,000/m(3)) and hyphae in coastal waters between Brisbane (27°S) and Sydney (34°S). These spores were successfully germinated from formalin-preserved samples, and using molecular sequencing of three different genes (the large subunit rRNA gene [LSU], internal transcribed spacer [ITS[, and beta-tubulin gene), they were conclusively identified as Aspergillus sydowii, an organism circumstantially associated with gorgonian coral fan disease in the Caribbean. Surprisingly, no human health or marine ecosystem impacts were associated with this Australian dust storm event. Australian fungal cultures were nontoxic to fish gills and caused a minor reduction in the motility of Alexandrium or Chattonella algal cultures but had their greatest impacts on Symbiodinium dinoflagellate coral symbiont motility, with hyphae being more detrimental than spores. While we have not yet seen any soft coral disease outbreaks on the Australian Great Barrier Reef similar to those observed in the Caribbean and while this particular fungal population was non- or weakly pathogenic, our observations raise the possibility of future marine ecosystem pathogen impacts from similar dust storms harboring more pathogenic strains.

Task-based assessment of resolution properties of CT images with a new index using deep convolutional neural network.

In this study, we propose a method for obtaining a new index to evaluate the resolution properties of computed tomography (CT) images in a task-based manner. This method applies a deep convolutional neural network (DCNN) machine learning system trained on CT images with known modulation transfer function (MTF) values to output an index representing the resolution properties of the input CT image [i.e., the resolution property index (RPI)]. Sample CT images were obtained for training and testing of the DCNN by scanning the American Radiological Society phantom. Subsequently, the images were reconstructed using a filtered back projection algorithm with different reconstruction kernels. The circular edge method was used to measure the MTF values, which were used as teacher information for the DCNN. The resolution properties of the sample CT images used to train the DCNN were created by intentionally varying the field of view (FOV). Four FOV settings were considered. The results of adapting this method to the filtered back projection (FBP) and hybrid iterative reconstruction (h-IR) images indicated highly correlated values with the MTF10% in both cases. Furthermore, we demonstrated that the RPIs could be estimated in the same manner under the same imaging conditions and reconstruction kernels, even for other CT systems, where the DCNN was trained on CT systems produced by the same manufacturer. In conclusion, the RPI, which is a new index that represents the resolution property using the proposed method, can be used to evaluate the resolution of a CT system in a task-based manner.

Sex differences in symptom presentation and their impact on diagnostic accuracy in Werner syndrome.

AIM: Whether sex differences exist in hereditary progeroid syndromes remains unclear. In this study, we investigated sex differences in patients with Werner syndrome (WS), a model of human aging, using patient data at the time of diagnosis. METHODS: The presence of six cardinal signs in the diagnostic criteria was retrospectively evaluated. RESULTS: We found that the percentage of patients with all cardinal signs was higher in males than in females (54.2% vs. 21.2%). By the age of 40 years, 57.1% of male patients with WS presented with all the cardinal signs, whereas none of the female patients developed all of them. In particular, the frequency of having a high-pitched, hoarse voice, a characteristic of WS, was lower in female patients. The positive and negative predictive values for clinical diagnosis were 100% for males and females, indicating the helpfulness of diagnostic criteria regardless of sex. More female patients than male (86.7% vs. 64%) required genetic testing for their diagnosis because their clinical symptoms were insufficient, suggesting the importance of genetic testing for females even if they do not show typical symptoms of WS. Finally, the frequency of abnormal voice was lower in patients with WS harboring the c.3139-1G > C homozygous mutation. CONCLUSION: These results indicate, for the first time, that there are sex differences in the phenotypes of hereditary progeroid syndromes. The analysis of this mechanism in this human model of aging may lead to the elucidation of sex differences in the various symptoms of normal human aging. Geriatr Gerontol Int 2024; 24: 161-167.

Serum anti­KIAA0513 antibody as a common biomarker for mortal atherosclerotic and cancerous diseases.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.